This invention relates to the determination of the concentration of sugar in the presence of interfering foreign substances, especially determination of glucose in a body fluid, in general, and more particularly to a method using an electrocatalytic sugar sensor comprising a measuring electrode, wherein the potential of the measuring electrode is alternatingly set to a reactivation and a measuring potential and the current flowing during the measuring period is evaluated as the measurement signal, as well as to an electrocatalytic sugar sensor for implementing this method.
The determination of the sugar concentration in a body fluid, especially the blood of a patient, is important, for instance, in the case of diabetics, since it is important for a diabetic that the normal blood glucose level be kept constant through the day. The blood glucose level can be influenced by the diet, by insulin injections and by motion therapy. It is essential in this connection that over or under compensation of the sugar content of the blood be avoided. For the patient himself it is important to know the prevailing blood sugar content, so that he can take suitable measures for controlling it if necessary.
Regulation of the glucose concentration automatically by means of a so-called artificial beta-cell has also been considered by controlling the insulin supply to the blood via a glucose sensor wherein insulin is always supplied to the blood, if desired, proportionally to a glucose reference value, when the glucose reference value is exceeded.
Heretofore, the glucose in the blood has generally been determined externally in a clinical laboratory by photometric means. However, electrochemical sensors are also known which make it possible to determine the glucose in the body fluid. In a so-called enzyme sensor, the glucose is oxidized to gluconic acid by means of glucose oxidase, wherein oxygen is consumed and hydrogen peroxide is formed. The oxygen consumption and the formation of hydrogen peroxide can be measured electrochemically, and a signal is thus obtained which is related to the glucose concentration. Since the enzyme sensor operates selectively and does not respond to foreign substances, it is possible to make a reproducible glucose determination, but it is not suitable for long term implantation because the enzymes, like all other proteins, decay under physiological conditions in the course of time; i.e., they are not stable over the long term under body conditions.
An electrocatalytic glucose sensor is known, for instance, from British patent specification No. 1,422,172. However, this sensor also is not stable over the long term if it is operated with potential control. With current controlled operation, on the other hand, the sensitivity is lower than desired.
While intermittent measurements have been possible heretofore with electrocatalytic glucose sensors, especially relative measurements (see in this connection: "Trans. Amer. Soc. Artif. Int. Organs", vol. XIX, 1973, pages 352 to 360) interference with the measurement signal still always takes place due to coreactants. For, impurities and accompanying substances can then either be oxidized at the measuring electrode and thereby falsify the measurement signal, or can limit the activity of the measuring electrode due to blocking. In the case of implantable sensors, furthermore, components of the body fluid, especially urea and amino acids, have been found to have an interfering effect, as they thwart a reproducible long-term measurement.
This applies in essence also to an implantable electrocatalytic glucose sensor which is described in the journal "Biomed. Technik", 22 (1977), pages 399 and 400. This sensor, which comprises a measuring electrode, counter electrode and reference electrode, is operated in accordance with the so-called voltage-jump method, i.e., a measuring and a reactivation potential are impressed alternatingly on the measuring electrode. During the measuring time, the current is integrated and at the end of the measuring time, this integral represents the measurement value.